Background: Treatment of high-risk NB within the major international cooperative groups (COG and SIOP) comprise intensive induction, consolidation with high dose chemotherapy and autologous stem cell rescue (ASCR) followed by anti-GD2 immunotherapy and isotretinoin as maintenance therapy. In the COG studies dinutuximab and cytokines (GM-CSF and IL-2) were used to treat patients in complete remission (CR) after ASCR whereas SIOPEN studies used dinutuximab-beta plus/minus IL-2 and included patients with responsive (no progression 109 days after ASCR) but refractory (skeletal metaiodobenzylguanidine positivity with three or fewer areas of abnormal uptake). Methods: Since December 2014, HR-NB patients referred to HSJD were eligible for consolidation with anti-GD2/GM-CSF immunotherapy in 2 consecutive studies (dinutuximab for EudraCT 2013-004864-69 and naxitamab for 017-001829-40) and naxitamab/GM-CSF compassionate use (CU) with or without prior ASCR. Patients were enrolled in 1st CR or with primary refractory bone/bone marrow (B/BM) disease. We accrued a study population of two groups whose consolidative therapy, aside from ASCR, was similar: anti-GD2 (dinutuximab or naxitamab) antibodies + GM-CSF and local radiotherapy. This is a retrospective analysis of their event-free survival (EFS) and overall survival (OS) calculated from study entry. Results: From Dec 14 til Dec 19, 67 study patients were treated with the COG (dinutuximab + GM-CSF+ IL-2 + RA) regimen (n = 21) in the HSJD-HRNB-Ch14.18 study or with Naxitamab and GM-CSF in the Ymabs study 201 (n = 12) or CU (n = 34). 23 patients were treated with primary refractory disease in the B/BM, and 44 in 1^st CR. The 67 study patients included 13 (19%) treated following single ASCR and 54 following induction chemotherapy and surgery. Median follow-up for all surviving patients is 16.2 months. Two-year rates for ASCR and non-ASCR patients were, respectively: EFS 64% vs. 54% (p = 0.28), and OS 66.7% vs. 84% (p = 0.8). For the 44 pts in 1^st CR, 2-year rates for ASCR and non-ASCR patients were, respectively: EFS 65% vs. 58% (p = 0.48), and OS 71% vs. 85% (p = 0.63). Conclusions: In this retrospective, single center study, ASCR did not provide survival benefit when anti-GD2 + GM-CSF based immunotherapy was used for consolidation after dose-intensive conventional chemotherapy.

Ymabs Therapeutics and United Therapeutics Institutional Funds